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. 2021 Apr 28;16(4):e0250774.
doi: 10.1371/journal.pone.0250774. eCollection 2021.

Sex differences in inflammatory markers in patients hospitalized with COVID-19 infection: Insights from the MGH COVID-19 patient registry

Emily S Lau  1   2 , Jenna N McNeill  1   3 , Samantha M Paniagua  1 , Elizabeth E Liu  1 , Jessica K Wang  1 , Ingrid V Bassett  4   5 , Caitlin A Selvaggi  6 , Steven A Lubitz  3 , Andrea S Foulkes  6 , Jennifer E Ho  1   2
Affiliations

Sex differences in inflammatory markers in patients hospitalized with COVID-19 infection: Insights from the MGH COVID-19 patient registry

Emily S Lau et al. PLoS One. .

Abstract

Background: Men are at higher risk for serious complications related to COVID-19 infection than women. More robust immune activation in women has been proposed to contribute to decreased disease severity, although systemic inflammation has been associated with worse outcomes in COVID-19 infection. Whether systemic inflammation contributes to sex differences in COVID-19 infection is not known.

Study design and methods: We examined sex differences in inflammatory markers among 453 men (mean age 61) and 328 women (mean age 62) hospitalized with COVID-19 infection at the Massachusetts General Hospital from March 8 to April 27, 2020. Multivariable linear regression models were used to examine the association of sex with initial and peak inflammatory markers. Exploratory analyses examined the association of sex and inflammatory markers with 28-day clinical outcomes using multivariable logistic regression.

Results: Initial and peak CRP were higher in men compared with women after adjustment for baseline differences (initial CRP: ß 0.29, SE 0.07, p = 0.0001; peak CRP: ß 0.31, SE 0.07, p<0.0001) with similar findings for IL-6, PCT, and ferritin (p<0.05 for all). Men had greater than 1.5-greater odds of dying compared with women (OR 1.71, 95% CI 1.04-2.80, p = 0.03). Sex modified the association of peak CRP with both death and ICU admission, with stronger associations observed in men compared with women (death: OR 9.19, 95% CI 4.29-19.7, p <0.0001 in men vs OR 2.81, 95% CI 1.52-5.18, p = 0.009 in women, Pinteraction = 0.02).

Conclusions: In a sample of 781 men and women hospitalized with COVID-19 infection, men exhibited more robust inflammatory activation as evidenced by higher initial and peak inflammatory markers, as well as worse clinical outcomes. Better understanding of sex differences in immune responses to COVID-19 infection may shed light on the pathophysiology of COVID-19 infection.

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Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Lubitz receives sponsored research support from Bristol Myers Squibb / Pfizer, Bayer AG, Boehringer Ingelheim, Fitbit, and IBM, and has consulted for Bristol Myers Squibb / Pfizer, Bayer AG, and Blackstone Life Sciences. Dr. Foulkes received sponsored research support from Bristol Myers Squibb and Fitbit. Dr. Ho has received research support from Gilead Sciences and Bayer AG, and research supplies from EcoNugenics. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. The association of inflammatory markers with death and ICU admission in men and women with COVID-19 infection.
* = sex*inflammatory marker pinteraction <0.05.
See this image and copyright information in PMC

References

    1. The COVID-19 Sex-Disaggregated Data Tracker 2020.
    1. Gebhard C, Regitz-Zagrosek V, Neuhauser HK, Morgan R, Klein SL. Impact of sex and gender on COVID-19 outcomes in Europe. Biology of sex differences. 2020;11(1):29. 10.1186/s13293-020-00304-9 - DOI - PMC - PubMed
    1. Channappanavar R, Fett C, Mack M, Ten Eyck PP, Meyerholz DK, Perlman S. Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection. Journal of immunology (Baltimore, Md: 1950). 2017;198(10):4046–53. 10.4049/jimmunol.1601896 - DOI - PMC - PubMed
    1. Scully EP, Haverfield J, Ursin RL, Tannenbaum C, Klein SL. Considering how biological sex impacts immune responses and COVID-19 outcomes. Nature reviews Immunology. 2020;20(7):442–7. 10.1038/s41577-020-0348-8 - DOI - PMC - PubMed
    1. Klein SL, Jedlicka A, Pekosz A. The Xs and Y of immune responses to viral vaccines. The Lancet Infectious diseases. 2010;10(5):338–49. 10.1016/S1473-3099(10)70049-9 - DOI - PMC - PubMed

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